Abstract：
BACKGROUND: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known.
OBJECTIVE: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer.
METHODS: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis.
CONCLUSIONS: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability.
CONCLUSIONS: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone.
RESULTS: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.
OBJECTIVE: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer.
METHODS: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis.
CONCLUSIONS: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability.
CONCLUSIONS: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone.
RESULTS: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.
摘要：
背景：在某些罕见致病性种系突变的携带者中，早发性和临床侵袭性前列腺癌的风险升高。在该人群中，使用多参数磁共振成像（MRI）增强传统的基于前列腺特异性抗原（PSA）的筛查措施的效用尚不清楚。
目的：评估基于MRI的筛查与传统的基于PSA的筛查在前列腺癌遗传风险升高的个体中的比较。
方法：招募年龄在35至74岁之间且无前列腺癌病史的19种前列腺癌风险基因中的任何一种致病/可能致病变异的男性种系携带者。干预登记的参与者接受了年度PSA筛查，直肠指检(DRE),和三年期多参数磁共振成像。DRE异常的个人，年龄调整后的PSA升高（35-49岁>1.5ng/ml，>2.0ng/ml，50-54年，55-74年>3.0ng/ml)，或可疑的多参数MRI（前列腺成像报告和数据系统[PI-RADS]≥3个病灶）进行前列腺活检。结果测量和统计分析终点是任何和临床上有意义的前列腺癌的诊断，通过决策曲线分析比较了替代筛查策略.
结论：迄今为止，101名男性完成了第一轮筛查。最大比例的参与者是BRCA2的携带者(n=44)，BRCA1(n=35),和ATM(n=7)变体。21人接受了活检,导致检测到9例癌症（7例具有临床意义）。为了检测有临床意义的前列腺癌，异常MRI（PI-RADS≥3）表现出100％的敏感性（7/7），阴性预测值（NPV）为100％，而仅基于PSA的筛查具有57%(4/7)的敏感性,NPV为73%.在决策曲线分析中评估的六种筛查策略中，与PSA筛查相比，仅基于MRI的筛查在所有阈值概率下都取得了更高的净收益-每7.5名患者中检测到1例额外的癌症病例。同时在相同的阈值概率下避免更多不必要的活检。
结论：前列腺癌相关致病种系突变携带者的疾病患病率较高。早期结果表明，基于MRI的筛查可以增强对临床重大疾病的早期检测，而不仅仅是PSA筛查。
结果：在这项研究中，我们介绍了PROGRESS前列腺癌筛查试验的中期结果.我们发现，在某些前列腺癌风险突变的种系携带者中，基于磁共振成像的筛查增强了前列腺癌的检测，同时减少了活检触发，与传统的前列腺特异性抗原筛查策略相比。
目的：评估基于MRI的筛查与传统的基于PSA的筛查在前列腺癌遗传风险升高的个体中的比较。
方法：招募年龄在35至74岁之间且无前列腺癌病史的19种前列腺癌风险基因中的任何一种致病/可能致病变异的男性种系携带者。干预登记的参与者接受了年度PSA筛查，直肠指检(DRE),和三年期多参数磁共振成像。DRE异常的个人，年龄调整后的PSA升高（35-49岁>1.5ng/ml，>2.0ng/ml，50-54年，55-74年>3.0ng/ml)，或可疑的多参数MRI（前列腺成像报告和数据系统[PI-RADS]≥3个病灶）进行前列腺活检。结果测量和统计分析终点是任何和临床上有意义的前列腺癌的诊断，通过决策曲线分析比较了替代筛查策略.
结论：迄今为止，101名男性完成了第一轮筛查。最大比例的参与者是BRCA2的携带者(n=44)，BRCA1(n=35),和ATM(n=7)变体。21人接受了活检,导致检测到9例癌症（7例具有临床意义）。为了检测有临床意义的前列腺癌，异常MRI（PI-RADS≥3）表现出100％的敏感性（7/7），阴性预测值（NPV）为100％，而仅基于PSA的筛查具有57%(4/7)的敏感性,NPV为73%.在决策曲线分析中评估的六种筛查策略中，与PSA筛查相比，仅基于MRI的筛查在所有阈值概率下都取得了更高的净收益-每7.5名患者中检测到1例额外的癌症病例。同时在相同的阈值概率下避免更多不必要的活检。
结论：前列腺癌相关致病种系突变携带者的疾病患病率较高。早期结果表明，基于MRI的筛查可以增强对临床重大疾病的早期检测，而不仅仅是PSA筛查。
结果：在这项研究中，我们介绍了PROGRESS前列腺癌筛查试验的中期结果.我们发现，在某些前列腺癌风险突变的种系携带者中，基于磁共振成像的筛查增强了前列腺癌的检测，同时减少了活检触发，与传统的前列腺特异性抗原筛查策略相比。
